Project 2: Determinants of Extreme Survival in Humans The reason why some humans live to extreme ages - some even in relatively good health - is largely unknown. This research project is designed to extend the "Longitudinal Study of Aging Danish Twins" (LSADT), to continue the follow-up of the Danish 1905-Cohort until its members turn 100, and to establish a cohort of 1,000 pairs of nonagenarian sisters. LSADT already comprises five in-person assessments among 70+ year old Danish twins and more than 4,500 twins have completed the intake assessment. We have assessed the Danish 1905-Cohort in 1998 and 2000 and a third wave will follow in 2003. Here we propose a final assessment in 2005 of the LSADT participants and the Danish 1905-Cohort. The assessment will closely follow previous assessments and include measures of physical, cognitive, health, and psychological functioning. An extra wave of LSADT will give us substantially more statistical power to disentangle the genetic and environmental components of healthy aging into higher ages and together with the Danish 1905-Cohort Study it will provide us with excellent power to perform association studies, survival analyses, and rate-of-change studies into extreme ages. The Danish 1905-Cohort Study will provide the first centenarian study in which both environmental and genetic information is available from a non-centenarian control group from the same birth cohort. To enhance the possibility of identifying new genetic factors of importance for healthy aging at extreme ages we propose a genome-wide linkage study using a cohort of 1,000 nonagenarian sisters ascertained using the unique Danish population registers. Denmark provides an ideal setting for such studies because of the existence of nationwide health and death registers covering practically all Danish citizens.